How and where to find NPS users: a cross national survey among current users of new psychoactive substances.

Use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes potentials and limitations of methods in a transnational survey of recent marginalized, nightlife and online community NPS users in Germany, Hungary, Ireland, the Netherlands, Poland and Portugal (n=3023). In terms of demographic profile, drug use history and type of NPS, different methods reached different segments of the NPS-using population. Last year use of different NPS varied across countries and groups. Respondents used NPS in a variety of settings, with public spaces most common in marginalized group. The study suggests that prevalence rates can reveal a picture of the NPS market that significantly deviates from what law enforcement seizures indicate. Outreach in nightlife settings and peer education are recommended to inform users about health risks and to improve access to drug services and care

A multilayered security infrastructure for connected vehicles : first lessons from the field

Connected vehicles are vulnerable to manipulation and a broad attack surface can be used to intrude in-vehicle networks from anywhere on earth. In this work, we present an integrated security infrastructure comprising network protection, monitoring, incident management, and counteractions, which we built into a prototype based on a production car. Our vehicle implements a Software-Defined Networking Ethernet backbone to restrict communication routes, network anomaly detection to make misbehavior evident, virtual controller functions to enable agile countermeasures, and an automotive cloud defense center to analyse and manage incidents on vehicle fleets. We present first measurements and lessons learned from operating the prototype: many network attacks can be prevented through software-defined access control in the backbone; anomaly detection can reliably detect misbehavior but needs to improve on false positive rate; controller virtualization needs tailored frameworks to meet in-car requirements; and cloud defence enables fleet management and advanced countermeasures. Our findings indicate attack mitigation times in the vehicle from 257 ms to 328 ms and from 2,168 ms to 2,713 ms traversing the cloud.ReviewPendin

Demo: A Security Infrastructure for Vehicular Information Using SDN, Intrusion Detection, and a Defense Center in the Cloud

Vehicular on-board communication is the basis for advanced driver assistance, autonomous driving, over-the-air updates, and many more. If unprotected, this infrastructure is vulnerable to manipulation and various attacks. As any networked system, future connected cars require robust protection, monitoring, and incidence management against cyber-attacks during their lifetime. We demonstrate an infrastructure that secures the in-vehicle communication system and enables the security management of an entire vehicle fleet. Our prototype-a real-world production car-uses an Ethernet backbone network. It implements protective measures using software-defined networking, anomaly detection technologies, and is connected to a cyber defense center in the cloud. We demonstrate how this combination can reliably detect and mitigate common attacks on the vehicle-including its legacy components

Parameterization of a single H-bond in Orange Carotenoid Protein by atomic mutation reveals principles of evolutionary design of complex chemical photosystems

Introduction: Dissecting the intricate networks of covalent and non-covalent interactions that stabilize complex protein structures is notoriously difficult and requires subtle atomic-level exchanges to precisely affect local chemical functionality. The function of the Orange Carotenoid Protein (OCP), a light-driven photoswitch involved in cyanobacterial photoprotection, depends strongly on two H-bonds between the 4-ketolated xanthophyll cofactor and two highly conserved residues in the C-terminal domain (Trp288 and Tyr201).Method: By orthogonal translation, we replaced Trp288 in Synechocystis OCP with 3-benzothienyl-L-alanine (BTA), thereby exchanging the imino nitrogen for a sulphur atom.Results: Although the high-resolution (1.8 Å) crystal structure of the fully photoactive OCP-W288_BTA protein showed perfect isomorphism to the native structure, the spectroscopic and kinetic properties changed distinctly. We accurately parameterized the effects of the absence of a single H-bond on the spectroscopic and thermodynamic properties of OCP photoconversion and reveal general principles underlying the design of photoreceptors by natural evolution.Discussion: Such “molecular surgery” is superior over trial-and-error methods in hypothesis-driven research of complex chemical systems

The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed

The seventh international RASopathies symposium:Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed

Visualizing the DNA repair process by a photolyase at atomic resolution

International audiencePhotolyases, a ubiquitous class of flavoproteins, use blue light to repair DNA photolesions. In this work, we determined the structural mechanism of the photolyase-catalyzed repair of a cyclobutane pyrimidine dimer (CPD) lesion using time-resolved serial femtosecond crystallography (TR-SFX). We obtained 18 snapshots that show time-dependent changes in four reaction loci. We used these results to create a movie that depicts the repair of CPD lesions in the picosecond-to-nanosecond range, followed by the recovery of the enzymatic moieties involved in catalysis, completing the formation of the fully reduced enzyme-product complex at 500 nanoseconds. Finally, back-flip intermediates of the thymine bases to reanneal the DNA were captured at 25 to 200 microseconds. Our data cover the complete molecular mechanism of a photolyase and, importantly, its chemistry and enzymatic catalysis at work across a wide timescale and at atomic resolution

Return to the sea, get huge, beat cancer: an analysis of cetacean genomes including an assembly for the humpback whale (Megaptera novaeangliae)

Cetaceans are a clade of highly specialized aquatic mammals that include the largest animals that have ever lived. The largest whales can have 1,000 more cells than a human, with long lifespans, leaving them theoretically susceptible to cancer. However, large-bodied and long-lived animals do not suffer higher risks of cancer mortality than humans—an observation known as Peto’s Paradox. To investigate the genomic bases of gigantism and other cetacean adaptations, we generated a de novo genome assembly for the humpback whale (Megaptera novaeangliae) and incorporated the genomes of ten cetacean species in a comparative analysis. We found further evidence that rorquals (family Balaenopteridae) radiated during the Miocene or earlier, and inferred that perturbations in abundance and/or the interocean connectivity of North Atlantic humpback whale populations likely occurred throughout the Pleistocene. Our comparative genomic results suggest that the evolution of cetacean gigantism was accompanied by strong selection on pathways that are directly linked to cancer. Large segmental duplications in whale genomes contained genes controlling the apoptotic pathway, and genes inferred to be under accelerated evolution and positive selection in cetaceans were enriched for biological processes such as cell cycle checkpoint, cell signaling, and proliferation. We also inferred positive selection on genes controlling the mammalian appendicular and cranial skeletal elements in the cetacean lineage, which are relevant to extensive anatomical changes during cetacean evolution. Genomic analyses shed light on the molecular mechanisms underlying cetacean traits, including gigantism, and will contribute to the development of future targets for human cancer therapies